Remicade

CENTOCOR

First biologic approved for ulcerative colitis

Infliximab, a chimeric monoclonal antibody, exerts its effect through inhibition of human tumor necrosis factor alpha (TNF alpha). Infliximab was approved on September 15, 2005, for reducing the signs and symptoms of disease, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to conventional therapy.

Safety. Serious, sometimes fatal, infections, including sepsis and pneumonia, have been reported in patients receiving TNF-blocking agents such as infliximab. The risk of these infections increases with concomitant immunosuppressive therapy. Tuberculosis (frequently disseminated or extra- pulmonary at clinical presentation), invasive fungal infections, and other opportunistic infections have also been observed in patients receiving infliximab. Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test, and treatment of latent tuberculosis infection should be initiated prior to therapy with infliximab. Infliximab should not be administered to patients with a clinically important, active infection, and caution should be exercised when considering the administration of infliximab to patients with a chronic infection or history of recurrent infection. Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving infliximab. Infliximab has been associated with adverse outcomes in patients with heart failure and should be used in these patients only after consideration of other treatment options. Infliximab has been associated with hypersensitivity reactions including urticaria, dyspnea, and/or hypotension, usually occurring within 2 hours of infusion. The administration of TNF-blocking agents with anakinra has been associated with an increased risk of serious infection and neutropenia. The most common adverse events associated with infliximab therapy include infections and infusion-related reactions.

Dosing. The recommended dose of infliximab for the treatment of ulcerative colitis is 5 mg/kg given as an induction regimen at 0, 2, and 6 weeks, followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter. Infliximab should be reconstituted with 10 mL of sterile water for injection, and the total dose of the reconstituted product must be further diluted to 250 mL with 0.9% sodium chloride injection. Infusion of infliximab should begin within 3 hours of preparation.